阿托伐他汀对博莱霉素致大鼠肺纤维化的抑制作用及其机制  

Inhibitory effect of atorvastatin on bleomycin-induced pulmonary fibrosis in rats and its mechanism

作　　者：袁颖[1] 陶振钢[2] 蔡映云[1] 胡予[1] 

机构地区：[1]复旦大学附属中山医院老年病科,上海200032 [2]复旦大学附属中山医院急诊科,上海200032

出　　处：《中华老年医学杂志》2015年第2期197-201,共5页Chinese Journal of Geriatrics

摘　　要：目的观察阿托伐他汀对博莱霉素所致大鼠肺纤维化的抑制作用及其机制，探讨防治肺纤维化的新途径。方法取SPF级雄性SD大鼠30只，随机分为生理盐水对照组、博莱霉素模型组、阿托伐他汀治疗组，每组各10只。生理盐水对照组气管内注人生理盐水0．2ml，其他2组气管内注入博莱霉素5mg／kg建立肺纤维化模型，此后阿托伐他汀治疗组每天给予阿托伐他汀10mg／kg灌胃，生理盐水对照组和博莱霉素模型组给予等量生理盐水灌胃。于第7天和第28天3组均各处死5只，苏木精-伊红（HE）染色法及Masson染色病理学观察肺泡炎性改变及肺纤维化改变；酶联免疫吸附法（ELISA）检测肺组织羟脯氨酸和肿瘤坏死因子-α（TNF-α）水平；Westernblot法检测肺组织Kruppel-样因子2（KLF2）的蛋白表达；采用实时聚合酶链反应（PCR）检测肺组织KLF2的mRNA表达。结果博莱霉素模型组与生理盐水对照组比较病理学检查显示，大鼠肺组织在第7天出现出血渗出等炎性反应，第28天出现纤维化；而阿托伐他汀治疗组第7天肺组织的炎性反应及第28天纤维化程度都比博莱霉素模型组明显减轻。与生理盐水对照组比较，博莱霉素模型组肺组织羟脯氨酸和TNF-α水平明显升高（均P〈0．05），而KLF2蛋白含量和KLF2-mRNA的表达均明显降低（均P〈o．05）；阿托伐他汀治疗组上述变化减轻，其肺组织的羟脯氨酸和TNF-α含量低于博莱霉素模型组（均P〈0．05），同时阿托伐他汀治疗组肺组织KLF2蛋白含量和KLF2-mRNA表达则高于博莱霉素模型组（均P〈0．05）。结论阿托伐他汀可减少炎性细胞分泌TNF-α、减轻博莱霉素导致的肺纤维化反应；其对于纤维化的抑制机制与上调KLF2mRNA表达有关。Objective To observe the inhibitory effect of atorvastatin on bleomycin-induced pulmonary fibrosis in SD rats and study their possible mechanism. Methods 30 male SD mice under SPF condition with average body weight of 250g were randomly allocated to three groups （n= 10, each） of saline control group （control group）, bleomycin-induced pulmonary fibrosis group （pulmonary fibrosis group） and atorvastatin treatment group （treatment group）. Bleomycin （5mg/kg） （versus 0.2 ml saline in control group） were endotracheally instilled in pulmonary fibrosis group and the treatment group in order to establish the model of pulmonary fibrosis. Subsequently, the rats in the treatment group received daily atorvastatin （10 mg/kg） orally. 5 rats in each group were sacrificed on 7th and 28th day after intratracheal instillation. Their lung tissues were taken and tested. The histological changes in the lungs were evaluated by hematoxylin-eosin and masson stain. The tumor necrosis factor （TNF-a） level and hydroxyproline content in lung tissues were measured by enzyme- linked immunosorbent assay （ELISA）. The expressions of Kruppel-like factor 2 （KLF2） protein and mRNA in lung tissues were measured by Western blotting and Real-Time PCR. Results The lung tissue in model group had significant bleeding and oozing inflammatory response on the 7th day and pulmonary fibrosis on the 28th day. Bleeding and oozing inflammatory response and pulmonary fibrosis were subdued in treatment group on the same days as compared to the model group. Hydroxyprolineand TNF-α contents in lung tissue were significantly higher in model group than in control group （both P〈0.05）. KLF2 protein and KLF2-mRNA expressions in lung tissues were significantly lower in model group than in control group （both P〈0.05）. The above changes were partially reversed in treatment group. Compared to model group, treatment group showed that hydroxyproline and TNF-α contents in lung tissues were significantly reduced （both P〈0.

关 键 词：肺纤维化 羟甲基戊二酰基COA还原酶抑制剂 Kruppel样转录因子类 

分 类 号：R965[医药卫生—药理学]